EP3368005A1 - Produits de soin buccal, et procédés associés - Google Patents

Produits de soin buccal, et procédés associés

Info

Publication number
EP3368005A1
EP3368005A1 EP16860635.8A EP16860635A EP3368005A1 EP 3368005 A1 EP3368005 A1 EP 3368005A1 EP 16860635 A EP16860635 A EP 16860635A EP 3368005 A1 EP3368005 A1 EP 3368005A1
Authority
EP
European Patent Office
Prior art keywords
composition
weight
partially hydrolyzed
fluoride
plant protein
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Granted
Application number
EP16860635.8A
Other languages
German (de)
English (en)
Other versions
EP3368005A4 (fr
EP3368005B1 (fr
Inventor
Latonya Kilpatrick-Liverman
Jianhong QIU
Lynette Zaidel
Thomas Subkowski
Stefan Jenewein
Marvin Karos
Claus Bollschweiler
Volker Wendel
Nina Schneider
Ralph Peter Santarpia
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
BASF SE
Colgate Palmolive Co
Original Assignee
BASF SE
Colgate Palmolive Co
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by BASF SE, Colgate Palmolive Co filed Critical BASF SE
Publication of EP3368005A1 publication Critical patent/EP3368005A1/fr
Publication of EP3368005A4 publication Critical patent/EP3368005A4/fr
Application granted granted Critical
Publication of EP3368005B1 publication Critical patent/EP3368005B1/fr
Active legal-status Critical Current
Anticipated expiration legal-status Critical

Links

Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00—Cosmetics or similar toiletry preparations
    • A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
    • A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
    • A61K8/64—Proteins; Peptides; Derivatives or degradation products thereof
    • A61K8/645—Proteins of vegetable origin; Derivatives or degradation products thereof
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00—Medicinal preparations containing peptides
    • A61K38/01—Hydrolysed proteins; Derivatives thereof
    • A61K38/011—Hydrolysed proteins; Derivatives thereof from plants
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00—Cosmetics or similar toiletry preparations
    • A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
    • A61K8/19—Cosmetics or similar toiletry preparations characterised by the composition containing inorganic ingredients
    • A61K8/20—Halogens; Compounds thereof
    • A61K8/21—Fluorides; Derivatives thereof
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00—Cosmetics or similar toiletry preparations
    • A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
    • A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
    • A61K8/33—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing oxygen
    • A61K8/34—Alcohols
    • A61K8/345—Alcohols containing more than one hydroxy group
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00—Cosmetics or similar toiletry preparations
    • A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
    • A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
    • A61K8/40—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing nitrogen
    • A61K8/41—Amines
    • A61K8/416—Quaternary ammonium compounds
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
    • A61P1/02—Stomatological preparations, e.g. drugs for caries, aphtae, periodontitis
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
    • A61Q11/00—Preparations for care of the teeth, of the oral cavity or of dentures; Dentifrices, e.g. toothpastes; Mouth rinses
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K2800/00—Properties of cosmetic compositions or active ingredients thereof or formulation aids used therein and process related aspects
    • A61K2800/40—Chemical, physico-chemical or functional or structural properties of particular ingredients
    • A61K2800/52—Stabilizers
    • A61K2800/524—Preservatives

Definitions

  • Dental enamel is a thin, hard layer of calcified material that covers the crown of teeth.
  • the major mineral component of dental enamel is hydroxyapatite, a crystalline form of calcium phosphate.
  • Chemical erosion of dental enamel may arise from tooth exposure to acidic food and drinks or to stomach acids arising from gastric reflux.
  • the erosion of dental enamel can lead to enhanced tooth sensitivity due to increased exposure of the dentin tubules and increased dentin visibility leading to the appearance of more yellow teeth.
  • the salivary pellicle a thin layer of salivary glycoproteins deposited on teeth
  • Acids are also generated in the oral cavity when plaque containing cariogenic bacteria metabolize carbohydrates. Since plaque forms a barrier controlling the kinetics of proton and mineral diffusion through the enamel, plaque acids cause carious lesions. Incorporating fluoride ions in dentifrice formulations is the most common method to mitigate the effects of plaque acids. Fluoride reduces the rate of demineralization and enhances remineralization. Several approaches have also been developed to stabilize calcium phosphate salts or control the plaque pH to enhance remineralization .
  • partially hydrolyzed plant proteins e.g., partially hydrolyzed proteins from wheat, rice, almond, potato, soya, pea or combinations thereof, for example partially hydrolyzed cereal proteins (hydrolyzed proteins from grains of the family Poaceae, for example partially hydrolyzed wheat protein or partially hydrolyzed rice protein, are effective in repairing or mitigating the effects of dental erosion, promoting dental remineralization, and enhancing the anti-cavity effects of fluoride.
  • partially hydrolyzed plant proteins e.g., partially hydrolyzed proteins from wheat, rice, almond, potato, soya, pea or combinations thereof
  • partially hydrolyzed cereal proteins hydrolyzed proteins from grains of the family Poaceae, for example partially hydrolyzed wheat protein or partially hydrolyzed rice protein
  • partially hydrolyzed plant proteins comprising oligo- and polypeptide molecules having a molecular weight distribution of about 500D to about 10000 D, e.g. 1000D to 5000 D are prepared for formulation with ingredients of a suitable orally acceptable carrier, by diluting in buffer, e.g., a phospate buffer such as Na2HP04 buffer (1.5 mM) and CaCl 2 (2.5 mM), to provide a buffered solution having a desired pH, e.g. pH 6-8, e.g., pH 7- 8, e.g., about pH 7.5, filtering and centrifuging the solution to obtain a filtrat comprising the partially hydrolyzed plant protein.
  • buffer e.g., phospate buffer such as Na2HP04 buffer (1.5 mM) and CaCl 2 (2.5 mM
  • a buffered solution having a desired pH, e.g. pH 6-8, e.g., pH 7- 8, e.g.,
  • a biocide for example cetylpyridinium chloride, e.g., at 0.1%) and/or fluoride may be added to the filtrate.
  • the partially hydrolyzed plant protein may then be combined with components of an orally acceptable carrier, for example a toothpaste or mouthwash base, to provide an oral care composition for repairing or mitigating the effects of dental erosion, promoting dental remineralization, and enhancing the anti-cavity effects of fluoride.
  • an orally acceptable carrier for example a toothpaste or mouthwash base
  • composition 1 for example a dentifrice, comprising:
  • the disclosure provides:
  • Composition 1 wherein the partially hydrolyzed plant protein is obtained from grains of the family Poaceae, e.g., is partially hydrolyzed maize (corn), wheat, rice, barley, oat, or millet protein.
  • Composition 1 wherein the partially hydrolyzed plant protein is obtained from wheat, rice, almond, potato, pea, soya or combinations thereof.
  • a desired pH e.g., pH 6-8, e.g., pH 7-8, e.g, by using a phosphate buffer.
  • any foregoing Composition wherein the partially hydrolyzed plant protein comprises a biocide, e.g., cetylpyridinium chloride (CPC) at an effective concentration, e.g., 0.1% by weight of the filtrate.
  • a biocide e.g., cetylpyridinium chloride (CPC) at an effective concentration, e.g., 0.1% by weight of the filtrate.
  • composition wherein the Composition comprises an effective amount of fluoride.
  • 2500 ppm for example, 250 ppm to 750 ppm, for example about 500 ppm fluoride.
  • Any foregoing Composition which comprises an amount of fluoride of 2500 ppm to 5000 ppm.
  • Any foregoing Composition comprising an orally acceptable zinc salt or oxide, for example selected from zinc oxide, zinc citrate, zinc lactate, zinc phosphate, zinc acetate, zinc chloride, zinc complexes with amino acids, and mixtures of any of the foregoing, for example wherein the amount of zinc is from 0.1 weight % to 3 weight %, e.g., about 1 to about 2 weight %, calculated by weight of zinc ion.
  • composition comprising an orally acceptable stannous salt, for example SnF2 or SnC12.
  • composition wherein the composition is in a form selected from a mouthrinse, a toothpaste, a tooth gel, a tooth powder, a non-abrasive gel, a mousse, a foam, a mouth spray, chewing gum, and a tablet, for example dentifrice, e.g., a toothpaste or mouthrinse.
  • a mouthrinse e.g., a toothpaste or mouthrinse.
  • composition further comprises one or more agents selected from: abrasives, pH modifying agents, surfactants, foam modulators, thickening agents, viscosity modifiers, humectants, anti-calculus or tartar control agents, sweeteners, flavorants and colorants.
  • agents selected from: abrasives, pH modifying agents, surfactants, foam modulators, thickening agents, viscosity modifiers, humectants, anti-calculus or tartar control agents, sweeteners, flavorants and colorants.
  • composition wherein the composition is a toothpaste.
  • composition comprising one or more soluble phosphate salts, for example wherein by "soluble phosphate salts” is meant an orally acceptable phosphate salt having a solubility in water of at least 1 g/lOOml at 25°C; for example wherein the one or more soluble phosphate salts are sodium and/or potassium salts of pyrophosphates and/or polyphosphates, e.g., tripolyphosphates; e.g., wherein the one or more soluble phosphate salts comprise tetrasodium pyrophosphate (TSPP), sodium tripolyphosphate (STPP) or a combination of TSPP and STPP; for example, whereon the one or more soluble phosphate salts are present in an amount of 1- 20%, e.g., 2-8%, e.g., ca. 5%, by weight of the composition.
  • soluble phosphate salts an orally acceptable phosphate salt having a solubility in water of at least 1 g/l
  • any foregoing Composition wherein the fluoride is provided by a salt selected from stannous fluoride, sodium fluoride, potassium fluoride, sodium monofluorophosphate, sodium fluorosilicate, ammonium fluorosilicate, amine fluoride (e.g., N'-octadecyltrimethylendiamine-N,N,N'- tris(2-ethanol)- dihydrofluoride), ammonium fluoride, titanium fluoride, hexafluorosulfate, and combinations thereof.
  • a salt selected from stannous fluoride, sodium fluoride, potassium fluoride, sodium monofluorophosphate, sodium fluorosilicate, ammonium fluorosilicate, amine fluoride (e.g., N'-octadecyltrimethylendiamine-N,N,N'- tris(2-ethanol)- dihydrofluoride), ammonium fluoride, titanium fluoride, hexafluorosul
  • Composition which is a dentifrice comprising a humectant, e.g., selected from glycerin, sorbitol, propylene glycol, polyethylene glycol, xylitol, and mixtures thereof, e.g. comprising at least 30%, e.g., 40-50% glycerin, by weight of the composition.
  • a humectant e.g., selected from glycerin, sorbitol, propylene glycol, polyethylene glycol, xylitol, and mixtures thereof, e.g. comprising at least 30%, e.g., 40-50% glycerin, by weight of the composition.
  • composition which is a dentifrice comprising one or more surfactants, e.g., selected from anionic, cationic, zwitterionic, and nonionic surfactants, and mixtures thereof, e.g., wherein the dentifrice base comprises an anionic surfactant, e.g., a surfactant selected from sodium lauryl sulfate, sodium ether lauryl sulfate, and mixtures thereof, e.g. in an amount of from about 0.3% to about 4.5% by weight, e.g. 1-2% sodium lauryl sulfate (SLS) by weight of the composition.
  • surfactants e.g., selected from anionic, cationic, zwitterionic, and nonionic surfactants, and mixtures thereof
  • the dentifrice base comprises an anionic surfactant, e.g., a surfactant selected from sodium lauryl sulfate, sodium ether lauryl sulfate, and mixtures thereof,
  • composition which is a dentifrice comprising a zwitterionic surfactant, for example a betaine surfactant, for example cocamidopropylbetaine, e.g. in an amount of from about 0.1% to about 4.5% by weight, e.g. 0.5-2% cocamidopropylbetaine by weight of the composition
  • composition which is a dentifrice comprising a viscosity modifying amount of one or more of polysaccharide gums, for example xanthan gum or carrageenan, silica thickener, and combinations thereof.
  • polysaccharide gums for example xanthan gum or carrageenan, silica thickener, and combinations thereof.
  • composition which is a dentifrice comprising gum strips or fragments.
  • Any foregoing Composition comprising flavoring, fragrance and/or coloring.
  • Any foregoing Composition which is a dentifrice comprising an effective amount of one or more antibacterial agents, for example comprising an antibacterial agent selected from halogenated diphenyl ether (e.g.
  • herbal extracts and essential oils e.g., rosemary extract, tea extract, magnolia extract, thymol, menthol, eucalyptol, geraniol, carvacrol, citral, hinokitol, catechol, methyl salicylate, epigallocatechin gallate, epigallocatechin, gallic acid, miswak extract, sea- buckthorn extract
  • bisguanide antiseptics e.g., chlorhexidine, alexidine or octenidine
  • quaternary ammonium compounds e.g., cetylpyridinium chloride (CPC), benzalkonium chloride, tetradecylpyridinium chloride (TPC), N-tetradecyl- 4-ethylpyridinium chloride (TDEPC)
  • phenolic antiseptics hexetidine, octenidine, sanguinarine, povidone iodine, delmopinol, saliflu
  • composition which is a dentifrice comprising a whitening agent, e.g., a selected from the group consisting of peroxides, metal chlorites, perborates, percarbonates, peroxyacids, hypochlorites, and combinations thereof; e.g. hydrogen peroxide or a hydrogen peroxide source, e.g., urea peroxide or a peroxide salt or complex (e.g., such as peroxyphosphate, peroxycarbonate, perborate, peroxysilicate, or persulphate salts; for example calcium peroxyphosphate, sodium perborate, sodium carbonate peroxide, sodium peroxyphosphate, and potassium persulfate).
  • a whitening agent e.g., a selected from the group consisting of peroxides, metal chlorites, perborates, percarbonates, peroxyacids, hypochlorites, and combinations thereof; e.g. hydrogen peroxide or a hydrogen peroxide source, e.g., urea
  • composition which is a dentifrice comprising an agent that interferes with or prevents bacterial attachment, e.g., solbrol or chitosan.
  • composition which is a dentifrice comprising a soluble calcium salt, e.g., selected from calcium sulfate, calcium chloride, calcium nitrate, calcium acetate, calcium lactate, and combinations thereof.
  • a soluble calcium salt e.g., selected from calcium sulfate, calcium chloride, calcium nitrate, calcium acetate, calcium lactate, and combinations thereof.
  • composition which is a dentifrice comprising a physiologically or orally acceptable potassium salt, e.g., potassium nitrate or potassium chloride, in an amount effective to reduce dentinal sensitivity.
  • a physiologically or orally acceptable potassium salt e.g., potassium nitrate or potassium chloride
  • composition which is a dentifrice comprising an anionic polymer, e.g., a synthetic anionic polymeric polycarboxylate, e.g., wherein the anionic polymer is selected from 1:4 to 4: 1 copolymers of maleic anhydride or acid with another polymerizable ethylenically unsaturated monomer; e.g., wherein the anionic polymer is a methyl vinyl ether/maleic anhydride (PVM/MA) copolymer having an average molecular weight (M.W.) of about 30,000 to about 1,000,000, e.g. about 300,000 to about 800,000, e.g., wherein the anionic polymer is about 1- 5%, e.g., about 2%, of the weight of the composition.
  • an anionic polymer e.g., a synthetic anionic polymeric polycarboxylate, e.g., wherein the anionic polymer is selected from 1:4 to 4: 1 copolymers of
  • composition which is a dentifrice comprising a breath freshener, fragrance or flavoring.
  • compositions wherein the pH of the composition is approximately neutral, e.g., pH 6-8, e.g., about pH 7.
  • Composition 1 is a dentifrice comprising
  • fluoride optionally an effective amount of fluoride; for example wherein fluoride is present in an amount of 100 ppm to 1500 ppm, for example, about 500 ppm; and c) an orally acceptable carrier.
  • composition 1A is a mouthwash (Composition 1A) comprising:
  • a) partially hydrolyzed plant protein comprising oligo- and polypeptide molecules having a molecular weight wherein at least 95% of the oligo- and polypeptide molecules are from about 500 to about 10000 D, e.g. about 1000 to about 5000 D; e.g. having a molecular weight distribution as follows: about 65% ⁇ 3500D, about 84-92% ⁇ 6000D, about 0.9- 3.6% > 9000D, and about 0.1-0.6% > 13000D;
  • the partially hydrolyzed plant protein is present in the composition in an amount of from 0.01 weight % to 3 weight % by total weight of the composition
  • Composition 1A wherein the partially hydrolyzed plant protein is obtained from grains of the family Poaceae, e.g., is partially hydrolyzed maize (corn), wheat, rice, barley, oat, or millet protein.
  • Composition 1A.1 wherein the partially hydrolyzed plant protein is partially hydrolyzed wheat protein or hydrolyzed rice protein.
  • composition 1A Any foregoing Composition 1A wherein the partially hydrolyzed plant protein is partially hydrolyzed wheat protein which is substantially free of gluten.
  • any foregoing Composition 1A, wherein the partially hydrolyzed plant protein is obtained from wheat, rice, almond, potato, pea, soya or combinations thereof.
  • 1A.5. Any foregoing Composition 1A wherein the partially hydrolyzed plant protein comprises fluoride.
  • composition 1A wherein the partially hydrolyzed plant protein has been adjusted to a desired pH, e.g., pH 6-8, e.g., pH 7-8, e.g, by using a phosphate buffer.
  • a desired pH e.g., pH 6-8, e.g., pH 7-8, e.g, by using a phosphate buffer.
  • composition 1A wherein the partially hydrolyzed plant protein comprises a biocide, e.g., cetylpyridinium chloride (CPC) at an effective concentration, e.g., 0.01 - 0.1% by weight of the filtrate.
  • a biocide e.g., cetylpyridinium chloride (CPC) at an effective concentration, e.g., 0.01 - 0.1% by weight of the filtrate.
  • composition 1A wherein the partially hydrolyzed plant protein is present in the composition in an amount of from 0.1 weight % to 3 weight % by total weight of the composition, e.g., 0.2 weight% to 2 weight%, e.g., about 0.2 weight %, by total weight of the composition.
  • Composition 1A comprises an effective amount of fluoride, e.g., a synergistically effective amount of fluoride, e.g., an amount of fluoride which in combination with the partially hydrolyzed plant protein, is effective to reduce or inhibit demineralization and/or enhance remineralization of the tooth enamel.
  • a synergistically effective amount of fluoride e.g., an amount of fluoride which in combination with the partially hydrolyzed plant protein, is effective to reduce or inhibit demineralization and/or enhance remineralization of the tooth enamel.
  • Composition 1A comprising an effective amount of fluoride from a fluoride ion source selected from stannous fluoride, sodium fluoride, potassium fluoride, sodium monofluorophosphate, sodium fluorosilicate, ammonium fluorosilicate, amine fluoride (e.g., N'-octadecyltrimethylendiamine-N,N,N'- tris(2- ethanol)-dihydrofluoride), ammonium fluoride, titanium fluoride, hexafluorosulfate, and combinations thereof.
  • a fluoride ion source selected from stannous fluoride, sodium fluoride, potassium fluoride, sodium monofluorophosphate, sodium fluorosilicate, ammonium fluorosilicate, amine fluoride (e.g., N'-octadecyltrimethylendiamine-N,N,N'- tris(2- ethanol)-dihydrofluoride), ammonium fluor
  • Composition 1A comprising a humectant, e.g., selected from glycerin, sorbitol, propylene glycol, polyethylene glycol, xylitol, and mixtures thereof, e.g., in an amount of 10-25% by weight, e.g. 18-20%,
  • a humectant e.g., selected from glycerin, sorbitol, propylene glycol, polyethylene glycol, xylitol, and mixtures thereof, e.g., in an amount of 10-25% by weight, e.g. 18-20%
  • Composition 1A comprising an anionic surfactant, for example sodium lauryl sulfate or sodium lauryl ether sulfate or mixtures thereof, e.g., in an amount of 0.01-0.5%, e.g., about 0.05% by weight.
  • an anionic surfactant for example sodium lauryl sulfate or sodium lauryl ether sulfate or mixtures thereof, e.g., in an amount of 0.01-0.5%, e.g., about 0.05% by weight.
  • Composition 1A comprising a nonionic surfactant, for example (i) a copolymer of propylene glycol and ethylene glycol, for example a triblock copolymer consisting of a central hydrophobic block of polypropylene glycol flanked by two hydrophilic blocks of polyethylene glycol, e.g., a poloxamer, e.g, poloxamer 188, poloxamer 338, poloxamer 407, or mixtures thereof, e.g., in an amount of 0.1-2% by weight, e.g., about 0.5%, and/or (ii) a polysorbate, for example, polysorbate 20, e.g., in an amount of 0.1-1% by weight, e.g., about 0.5%, and/or (iii) a polyethoxylated vegetable oil, e.g., polyoxyl 40 hydrogenated castor oil, e.g., in an amount of 0.05-0.
  • Composition 1A comprising a breath freshener, fragrance or flavoring.
  • composition 1A wherein the pH of the composition is approximately neutral, e.g., pH 6-8, e.g., about pH 7.
  • composition 1 A comprising partially hydrolyzed wheat protein, e.g.
  • Composition 1A which is substantially free of ethanol, e.g. having less than 0.5% ethanol by weight.
  • a) partially hydrolyzed wheat protein e.g. in an amount of from 0.05-1% by weight, e.g., about 0.2%
  • a fluoride ion source providing 200 to 1000 ppm fluoride, e.g., about 225 ppm or about 500 ppm fluoride, and
  • cetylpyridinium chloride e.g. in an amount of 0.01%-0.1% by weight, e.g., about 0.04%.
  • composition 1A which is a mouthwash comprising
  • a) partially hydrolyzed wheat protein e.g. in an amount of from 0.05-1% by weight, e.g., about 0.2%
  • a fluoride ion source e.g., providing 200 to 1000 ppm fluoride, e.g., about 225 ppm or about 500 ppm fluoride,
  • cetylpyridinium chloride e.g. in an amount of 0.01%-0.1% by weight, e.g., about 0.04%
  • nonionic surfactant e.g. poloxamer, e.g. in an amount of 0.1-1% by weight, e.g., about 0.5%
  • humectant e.g. comprising sorbitol, glycerin, propylene glycol, and/or mixtures of any two or more of those, in an amount of 10-25% by weight, e.g. 18-20%, f) sweetener and flavorings,
  • a preservative e.g. potassium sorbate, e.g., in an amount of 0.01- 0.1% by weight, e.g., about 0.05%, and
  • Composition 1 A for use to reduce and inhibit acid erosion, clean the teeth, reduce bacterially-generated biofilm and plaque, reduce gingivitis, inhibit tooth decay and formation of cavities, and reduce dentinal hypersensitivity.
  • Composition 1A for use in enhancing the anti-cavity and repair effects of fluoride.
  • the disclosure provides any of Compositions 1, et seq. for use in repairing or inhibiting dental erosion, promoting remineralization , and/or enhancing the anti-cavity effects of fluoride; for example for use in any of the following methods according to Method 1, et seq.
  • the disclosure provides a method (Method 1) of repairing or inhibiting dental erosion, promoting dental remineralization , and/or enhancing the anti-cavity effects of fluoride comprising applying to the teeth a composition, e.g., any of Composition 1, et seq. for example, any of Composition 1A, et seq., for example an oral care composition comprising: a) partially hydrolyzed plant protein, comprising oligo- and polypeptide molecules having a molecular weight wherein at least 95% of the plant protein is from about 500 to about 10000 D, e.g. about 1000 to about 5000 D; e.g. having a molecular weight distribution as follows: about 65% ⁇ 3500D, about 84-92% ⁇ 6000D, about 0.9-3.6% > 9000D, and about 0.1-0.6% > 13000D; and
  • the disclosure provides:
  • Method 1 wherein the partially hydrolyzed plant protein is obtained from wheat, rice, almond, potato, pea, soya or combinations thereof; for example from grains of the family Poaceae, e.g., is partially hydrolyzed maize (corn), wheat, rice, barley, oat, or millet protein.
  • the partially hydrolyzed plant protein is obtained from wheat, rice, almond, potato, pea, soya or combinations thereof; for example from grains of the family Poaceae, e.g., is partially hydrolyzed maize (corn), wheat, rice, barley, oat, or millet protein.
  • Method 1.1 wherein the partially hydrolyzed plant protein is partially hydrolyzed wheat protein or hydrolyzed rice protein.
  • Method 1 wherein the partially hydrolyzed plant protein is obtained from almond, potato or soya.
  • any foregoing Method wherein the partially hydrolyzed plant protein comprises fluoride. Any foregoing Method wherein the partially hydrolyzed plant protein has been adjusted to the desired pH, e.g., pH 6-8, for example pH 7-8, e.g., using a phosphate buffer.
  • the partially hydrolyzed plant protein comprises a biocide, e.g., cetylpyridinium chloride (CPC) at an effective concentration, e.g., 0.1% by weight of the filtrate.
  • a biocide e.g., cetylpyridinium chloride (CPC) at an effective concentration, e.g., 0.1% by weight of the filtrate.
  • composition wherein the Composition comprises an effective amount of fluoride.
  • any foregoing Method wherein the amount of fluoride is 100 ppm to 1000 ppm, for example, about 500 ppm fluoride.
  • composition is in a form selected from a mouthrinse, a toothpaste, a tooth gel, a tooth powder, a non-abrasive gel, a mousse, a foam, a mouth spray, and a tablet.
  • composition further comprises one or more agents selected from: abrasives, pH modifying agents, surfactants, foam modulators, thickening agents, viscosity modifiers, humectants, anti-calculus or tartar control agents, sweeteners, flavorants and colorants.
  • agents selected from: abrasives, pH modifying agents, surfactants, foam modulators, thickening agents, viscosity modifiers, humectants, anti-calculus or tartar control agents, sweeteners, flavorants and colorants.
  • composition is a dentifrice, e.g., a toothpaste.
  • composition is selected from any of Compositions 1, et seq., supra.
  • Any foregoing Method which is a method for reducing, inhibiting or repairing dental erosion, for example erosion of the enamel, for example wherein the composition is applied to the teeth of a patient having been identified as having dental erosion or being at elevated risk of having dental erosion. 1.15.
  • Any foregoing Method which is a method for promoting dental remineralization, for example remineralization of the enamel, for example wherein the composition is applied to the teeth of a patient having been identified as having demineralization.
  • Method 1.16 wherein the composition comprises an effective amount of fluoride and/or wherein the method further comprises administration of an oral care product comprising an effective amount of fluoride mouth rinse or toothpaste comprising an effective amount of fluoride.
  • composition is selected from any of
  • composition is selected from any of
  • Composition 1A et seq.
  • the disclosure provides the use of a partially hydrolyzed plant protein, for example a partially hydrolyzed wheat protein or partially hydrolyzed rice protein, in the manufacture of an oral care composition, for example according to any of Compositions 1, et seq., e.g., any of Compositions 1A, et seq., for repairing or inhibiting dental erosion, promoting remineralization, and/or enhancing the anti-cavity effects of fluoride, e.g., in any of Methods 1, et seq.
  • a partially hydrolyzed plant protein for example a partially hydrolyzed wheat protein or partially hydrolyzed rice protein
  • the disclosure provides a method (Method 2) of making an oral care product, e.g. an oral care product useful for repairing or inhibiting dental erosion, promoting dental remineralization , and/or enhancing the anti-cavity effects of fluoride, e.g., a product according to any of Composition 1, et seq., e.g., any of Composition 1A, et seq., comprising
  • a) a partially hydrolyzed plant protein comprising oligo- and polypeptide molecules having a molecular weight distribution of about 500 to about 10000 D, e.g. about 1000 to about 5000 D, adjusting the pH by dilution with an aqueous buffer solution, e.g., a phosphate buffer solution, e.g., to obtain a solution having the desired pH, e.g., pH 6-8, e.g., pH 7-8; b) filtering and centrifuging the solution product of a) to obtain a filtrate comprising the partially hydrolyzed plant protein;
  • an aqueous buffer solution e.g., a phosphate buffer solution
  • fluoride e.g., in the form of an orally acceptable salt containing fluoride, for example sodium fluoride or sodium monofluorophosphate
  • a biocide e.g., cetylpyridinium chloride at an effective amount, e.g., 0.01 to 1%, e.g., about 0.1% by weight of the filtrate
  • an oral care composition comprising the partially hydrolyzed plant protein in an amount of from 0.01 weight % to 3 weight % by total weight of the composition.
  • the disclosure provides:
  • Method 2 wherein the partially hydrolyzed plant protein is obtained from wheat, rice, almond, potato, pea, soya or combinations thereof, for example from grains of the family Poaceae, e.g., is partially hydrolyzed maize (corn), wheat, rice, barley, oat, or millet protein.
  • the partially hydrolyzed plant protein is obtained from wheat, rice, almond, potato, pea, soya or combinations thereof, for example from grains of the family Poaceae, e.g., is partially hydrolyzed maize (corn), wheat, rice, barley, oat, or millet protein.
  • Method 2.1 wherein the partially hydrolyzed plant protein is partially hydrolyzed wheat protein or hydrolyzed rice protein.
  • Method 2 wherein the partially hydrolyzed plant protein is obtained from almond, potato or soya.
  • composition is a composition according to any of Composition 1, et seq.
  • composition is a composition according to any of Composition 1A, et seq.
  • the disclosure provides an oral care composition comprising partially hydrolyzed plant protein, e.g., a composition according to any of Composition 1, et seq., for example any of Composition 1A, et seq., wherein the oral care composition is obtained or obtainable by the process of Method 2, et seq.
  • Hydrolyzed plant proteins are proteins from plants, for example, from edible plant parts, for example from wheat, rice, almond, potato, pea, soya or combinations thereof, e.g., from cereal grains such as maize, wheat, rice, barley, oats, and millet.
  • the hydrolyzed plant proteins are from wheat or rice.
  • Hydrolyzed wheat protein is typically obtained by enzymatically hydrolyzing wheat proteins using endoproteases and exoproteases. Hydrolyzed wheat protein may also be obtained through acid or alkaline hydrolysis. Methods of preparing hydrolyzed wheat protein would be known to the person skilled in the art of protein chemistry. However, hydrolyzed wheat protein is also commercially available as Gluadin ® W20, Gluadin W40 from BASF, and as Wheatpro ® from IKEDA.
  • Gluadin W20 is a partial hydrolysate obtained through enzymatic hydrolysis of wheat gluten. It contains at least 20.0 % of dry substance.
  • Gluadin W40 is a partial hydrolysate obtained through enzymatic hydrolysis of wheat gluten. It contains at least 40.0 % of dry substance.
  • the hydrolyzed plant protein is made from processed wheat protein which is free of gluten.
  • Hydrolyzed rice protein is typically obtained by enzymatically hydrolyzing rice protein using endoproteases and exoproteases. Hydrolyzed rice protein may also be obtained through acid or alkaline hydrolysis. Methods of preparing hydrolyzed rice protein would be known to the person skilled in the art of protein chemistry. However, hydrolyzed rice protein is also commercially available as Gluadin ® R from BASF, and as Rice Pro-Tein BK-S ® from TRI-K Industries [0024] The hydrolyzed plant protein used in the compositions and methods herein is not fully hydrolyzed and thus is sometimes referred to as "partially hydrolyzed" to emphasize this point.
  • the hydrolyzed plant protein typically comprises a mixture of amino acids and peptides of varying size.
  • MW of relevant active ingredient is in the range of about 500 - about 10,000 D, for example about 1000 to about 5000 D.
  • the hydrolyzed plant protein is present in the composition in an amount of from 0.01 weight % to 3 weight % by total weight of the composition. In some embodiments, the hydrolyzed plant protein is present in the composition in an amount of from 0.1 weight % to 3 weight %, or from 0.1 weight % to 2 weight %, or from 0.1 weight % to 1 weight % by total weight of the composition.
  • the hydrolyzed plant protein is present in the composition in an amount of from 0.05 weight % to 1 weight %, or from 0.1 weight % to 0.5 by total weight of the composition. In further embodiments, the hydrolyzed plant protein is present in the composition in an amount of from 0.5 weight % to 3 weight %, or from 0.5 weight % to 2 weight %, or from 0.5 weight % to 1 weight % by total weight of the composition. In still further embodiments, the hydrolyzed plant protein is present in the composition in an amount of from 1 weight % to 3 weight %, or from 1 weight % to 2 weight % by total weight of the composition.
  • the compositions of the present invention comprise both hydrolyzed wheat protein and hydrolyzed rice protein.
  • the hydrolyzed wheat protein and the hydrolyzed rice protein may be present in the composition in the amounts defined above.
  • the total amount of hydrolyzed wheat protein and hydrolyzed rice protein in the composition is from 0.1 weight % to 3 weight %, or from 0.1 weight % to 2 weight %, or from 0.1 weight % to 1 weight %, or from 0.1 weight % to 0.5 weight % by total weight of the composition.
  • the total amount of hydrolyzed wheat protein and hydrolyzed rice protein in the composition is from 1 weight % to 3 weight %, or from 1 weight % to 2 weight %, by total weight of the composition.
  • orally acceptable carrier denotes a carrier made from materials that are safe and acceptable for oral use in the amounts and concentrations intended, for example materials as would be found in conventional toothpaste and mouthwash. Such materials include water or other solvents that may contain a humectant such as glycerin, sorbitol, xylitol and the like.
  • orally acceptable carrier encompasses all of the components of the oral care composition except for the hydrolyzed plant protein and the fluoride.
  • the term refers to inert or inactive ingredients that serve to deliver the hydrolyzed plant protein, and/or any other functional ingredients, to the oral cavity.
  • Orally acceptable carriers for use in the invention include conventional and known carriers used in making mouth rinses or mouthwashes, toothpastes, tooth gels, tooth powder, lozenges, gums, beads, edible strips, tablets and the like. Carriers should be selected for compatibility with each other and with other ingredients of the composition.
  • the carrier is typically a water/humectant system that provides a major fraction by weight of the composition.
  • the carrier component of a toothpaste composition may comprise water, one or more humectants, and other functional components other than the hydrolyzed wheat protein or hydrolyzed rice protein.
  • the carrier is typically a water/alcohol liquid mixture in which the hydrolyzed wheat protein or hydrolyzed rice protein is dissolved or dispersed.
  • the carrier typically comprises a solid matrix material that dissolves slowly in the oral cavity.
  • the carrier typically comprises a gum base, while in an edible strip, the carrier typically comprises one or more film forming polymers.
  • the oral care compositions provided herein may further comprise one or more additional ingredients selected from abrasives, pH modifying agents, surfactants, foam modulators, thickening agents, viscosity modifiers, humectants, anti-calculus or tartar control agents, sweeteners, flavorants, colorants and preservatives. These ingredients may also be regarded as carrier materials. Non-limiting examples are provided below.
  • a composition of the invention comprises at least one abrasive, useful, for example, as a polishing agent.
  • abrasive useful, for example, as a polishing agent.
  • Any orally acceptable abrasive can be used, but the type, fineness (particle size) and amount of abrasive should be selected so that tooth enamel is not excessively abraded during normal use of the composition.
  • Suitable abrasives include, without limitation, silica, for example in the form of silica gel, hydrated silica or precipitated silica, alumina, insoluble phosphates, calcium carbonate, resinous abrasives such as urea-formaldehyde condensation products and the like.
  • insoluble phosphates useful as abrasives are orthophosphates, polymetaphosphates and pyrophosphates.
  • Illustrative examples are dicalcium orthophosphate dihydrate, calcium pyrophosphate, [beta] -calcium pyrophosphate, tricalcium phosphate, calcium polymetaphosphate and insoluble sodium polymetaphosphate.
  • One or more abrasives are optionally present in the oral care compositions of the present invention in an amount of 1 weight % to 5 weight % by total weight of the composition.
  • the average particle size of an abrasive, if present, is generally 0.1 to 30 ⁇ , and preferably, 5 to 15 ⁇ .
  • an oral care composition of the invention comprises at least one bicarbonate salt, useful, for example, to impart a "clean feel" to teeth and gums due to effervescence and release of carbon dioxide.
  • bicarbonate salt useful, for example, to impart a "clean feel" to teeth and gums due to effervescence and release of carbon dioxide.
  • Any orally acceptable bicarbonate can be used, including, without limitation, alkali metal bicarbonates such as sodium and potassium bicarbonates, ammonium bicarbonate and the like.
  • One or more bicarbonate salts are optionally present in a total amount of 1 weight % to 10% by weight of the composition.
  • an oral care composition of the invention comprises at least one pH modifying agent.
  • pH modifying agents include acidifying agents to lower pH, basifying agents to raise pH and buffering agents to control pH within a desired range.
  • one or more compounds selected from acidifying, basifying and buffering agents can be included to provide a pH of 2 to 10, or in various illustrative embodiments a pH of 2 to 8, 3 to 9, 4 to 8, 5 to 7, 6 to 10, or 7 to 9.
  • Any orally acceptable pH modifying agent can be used, including, without limitation, carboxylic, phosphoric and sulfonic acids, acid salts (for example, monosodium citrate, disodium citrate, monosodium malate), alkali metal hydroxides such as sodium hydroxide, carbonates such as sodium carbonate, bicarbonates, borates, silicates, phosphates (for example, monosodium phosphate, trisodium phosphate, pyrophosphate salts) imidazole and the like.
  • acid salts for example, monosodium citrate, disodium citrate, monosodium malate
  • alkali metal hydroxides such as sodium hydroxide
  • carbonates such as sodium carbonate, bicarbonates, borates, silicates
  • phosphates for example, monosodium phosphate, trisodium phosphate, pyrophosphate salts
  • imidazole imidazole and the like.
  • One or more pH modifying agents are optionally
  • a composition of the invention comprises at least one surfactant, useful, for example, to provide enhanced stability to the composition and the components contained therein, to aid in cleaning a dental surface through detergent action, and to provide foam upon agitation (for example, during brushing with a dentifrice composition of the invention).
  • Any orally acceptable surfactant including those which are anionic, nonionic or amphoteric, can be used.
  • Suitable anionic surfactants include, without limitation, water-soluble salts of Cs-20 alkyl sulfates, sulfonated monoglycerides of Cs-20 fatty acids, sarcosinates, taurates and the like.
  • Suitable nonionic surfactants include, without limitation, poloxamers, polyoxyethylene sorbitan esters, fatty alcohol ethoxylates, alkylphenol ethoxylates, tertiary amine oxides, tertiary phosphine oxides, dialkyl sulfoxides and the like.
  • Suitable amphoteric surfactants without limitation, derivatives of Cs-20 aliphatic secondary and tertiary amines having an anionic group such as carboxylate, sulfate, sulfonate, phosphate or phosphonate.
  • a suitable example is cocoamidopropyl betaine.
  • One or more surfactants are optionally present in a total amount of 0.01 weight % to 10 weight %, for example, from 0.05 weight % to 5 weight % or from 0.1 weight % to 2 weight % by total weight of the composition.
  • an oral care composition of the invention comprises at least one foam modulator, useful, for example, to increase the amount, thickness or stability of foam generated by the composition upon agitation.
  • foam modulator can be used including, without limitation, polyethylene glycols (PEGs).
  • PEGs polyethylene glycols
  • One or more PEGs are optionally present in a total amount of from 0.1 weight % to 10 weight by total weight of the composition.
  • an oral care composition of the invention comprises at least one thickening agent, useful, for example, to impart a desired consistency and/or mouth feel to the composition.
  • Any orally acceptable thickening agent can be used including, without limitation, carbomers (carboxyvinyl polymers), carrageenans, cellulosic polymers such as hydroxyethylcellulose, carboxymethylcellulose (CMC) and salts thereof, natural gums such as karaya, xanthan, gum arabic and tragacanth, colloidal magnesium aluminum silicate, colloidal silica and the like.
  • One or more thickening agents are optionally present in a total amount of 0.01 weight % to 15 weight %, by total weight of the composition.
  • a composition of the invention comprises at least one viscosity modifier, useful, for example, to inhibit settling or separation of ingredients or to promote re- dispersion of ingredients upon agitation of a liquid composition.
  • Any orally acceptable viscosity modifier can be used including, without limitation, mineral oil, petrolatum, clays, silica and the like.
  • One or more viscosity modifiers are optionally present in a total amount of 0.01 weight % to 10 weight %, by total weight of the composition.
  • an oral care composition of the invention comprises at least one humectant which may be used to prevent hardening of a toothpaste upon exposure to air, or in the case of a mouthwash, to provide improved moisturizing and mouthfeel and enhance the miscibility of poorly soluble components such a flavoring oils.
  • Any orally acceptable humectant can be used, including, without limitation, polyhydric alcohols such as glycerin, sorbitol, xylitol or low molecular weight PEGs. Most humectants also function as sweeteners.
  • One or more humectants are optionally present in a total amount of 1 weight % to 50 weight % by total weight of the composition.
  • an oral care composition of the invention comprises at least one sweetener which enhances taste of the composition.
  • Any orally acceptable natural or artificial sweetener can be used including, without limitation, dextrose, sucrose, maltose, dextrin, mannose, xylose, ribose, fructose, levulose, galactose, corn syrup, partially hydrolyzed starch, hydrogenated starch hydrolysate, sorbitol, mannitol, xylitol, maltitol, isomalt, aspartame, neotame, saccharin and salts thereof, dipeptide-based intense sweeteners, cyclamates and the like.
  • One or more sweeteners are optionally present in a total amount of 0.005 weight % to 5 weight % by total weight of the composition.
  • an oral care composition of the invention comprises at least one flavorant which enhances the taste of the composition.
  • Any orally acceptable natural or synthetic flavorant can be used including, without limitation, vanillin, sage, marjoram, parsley oil, spearmint oil, cinnamon oil, oil of wintergreen (methylsalicylate), peppermint oil, clove oil, bay oil, anise oil, eucalyptus oil, citrus oils, fruit oils and essences, and the like.
  • ingredients that provide fragrance and/or other sensory effects in the mouth including cooling or warming effects.
  • Such ingredients illustratively include menthol, menthyl acetate, menthyl lactate, camphor, eucalyptus oil, eucalyptol, eugenol, cassia, oxanone, a-irisone, thymol, linalool, benzaldehyde, cinnamaldehyde, N-ethyl- /?-menthan-3-carboxamine, N,2,3- trimethyl-2-isopropylbutanamide, 3 -( 1 -menthoxy)-propane- 1 ,2-diol, cinnamaldehyde glycerol acetal (CGA), menthone glycerol acetal (MGA) and the like.
  • One or more flavorants are optionally present in a total amount of 0.01 weight % to 5 weight %, by total weight of the composition.
  • an oral care composition of the invention comprises at least one colorant.
  • a colorant can serve a number of functions. These include providing a white or light- colored coating on a dental surface, indicating locations on a dental surface that have been effectively contacted by the composition, and/or modifying the appearance of the composition to enhance attractiveness to the consumer.
  • Any orally acceptable colorant can be used including, without limitation, talc, mica, magnesium carbonate, calcium carbonate, magnesium silicate, magnesium aluminum silicate, silica, titanium dioxide, zinc oxide, iron oxide, ferric ammonium ferrocyanide, manganese violet, titaniated mica, bismuth oxychloride and the like.
  • One or more colorants are optionally present in a total amount of 0.001 weight % to 20 weight % by total weight of the composition.
  • an oral care composition of the invention comprises a preservative.
  • the preservative may be selected from parabens, potassium sorbate, benzyl alcohol, phenoxyethanol, polyaminopropryl biguanide, caprylic acid, sodium benzoate and cetylpyridinium chloride.
  • the preservative is present at a concentration of from about 0.001 to about 1 weight %, by total weight of the composition.
  • compositions of the invention and their uses.
  • the exemplified compositions are illustrative and do not limit the scope of the invention.
  • Bovine teeth are cut, ground and polished to obtain enamel blocks having approximate dimensions of 3mm x 3mm x 2mm.
  • the thickness of the enamel is approximately 1 to 2mm, and the thickness of dentin is approximately 1mm. All measurements are taken on the enamel surface.
  • the surface roughness of enamel blocks is measured before and after acid etching. Acid etching is achieved by placing the enamel blocks in 1% citric acid solution (pH 3.8) until the surface roughness (Sq) reaches 100 - 200. This Sq value is recorded as the surface roughness of etched enamel.
  • a hydrolyzed wheat protein preparation is made using GLUADIN W20 from BASF.
  • the hydrolysate is diluted to the final concentration using a Na 2 HP04 buffer (1.5 mM) and CaCl 2 (2.5 mM). After neutralizing to a pH of 7.5, the solution is filtered and centrifuged. Acid-etched enamel blocks are subsequently incubated with a solution comprising the treated hydrolyzed wheat protein at a concentration of 0.5 weight % (2ml solution per block) for 60 minutes.
  • the enamel blocks are incubated in artificial saliva (AS) solution (0.4g NaCl, 0.4g KC1, 0.8g CaCl 2 , 0.69g NaH 2 P0 4 , lg urea, 1 liter distilled water; pH 7 (adjusted using 1M NaOH)) for 22 hours.
  • the enamel blocks are then treated a second time with the hydrolyzed protein solution, and incubated again with artificial saliva for 22 hours.
  • the blocks are then rinsed with deionized (DI) water and air-dried prior to measuring their surface roughness.
  • Enamel blocks treated with 0.5% PBS are used as a negative control for the experiment.
  • the results are illustrated in Table 1.
  • the % remineralization represents the % reduction in final surface roughness (Sq) relative to surface roughness of etched enamel (before treatment and artificial saliva incubation):
  • hydrolyzed wheat protein is effective in reducing the surface roughness of acid-etched enamel blocks at a concentration of 0.5 weight %.
  • Enamel blocks are prepared as described in Example 1. Acid-etching is achieved by placing the enamel blocks in 1% citric acid solution (pH 3.8) for 15 minutes. The nanohardness and Young's modulus at 500nm depth are measured prior to and after etching. Etched enamel blocks are incubated with a solution of hydrolyzed wheat protein (GLUADIN W20), at a concentration of 0.5 weight %, for 30 minutes (2ml solution/block), followed by an incubation with AS solution as described in Example 1, for 22 to 24 hours. The hydrolyzed wheat protein and AS incubation steps are repeated two additional times, after which the enamel blocks are rinsed with DI water and air-dried.
  • GLUADIN W20 hydrolyzed wheat protein
  • the nanohardness and Young's modulus of the treated enamel blocks are measured at 500nm depth to assess the enamel repair effects of the hydrolyzed wheat protein.
  • a solution of 500 ppm fluoride is used as a positive control for the experiment. The results are illustrated in Tables 2 and 3.
  • hydrolyzed wheat protein is effective in repairing acid-eroded enamel.
  • Enamel blocks are prepared as described in Example 1. Microhardness is measured using a Micromet 6020 Micro-hardness Tester with a Knoop Diamond Indenter and a 50 g load (Buehler, Lake Bluff, IL, USA). Blocks with a Knoop hardness (KH) of at least 300 are selected. The blocks are etched by immersing in 30% phosphoric acid for 15 seconds. The KH on the left and right sides of the blocks are measured.
  • KH Knoop hardness
  • the right side of the blocks are covered with tape prior to treating the blocks with 20mg/ml solution of hydrolyzed wheat protein (Gluadin W20 from BASF) or hydrolyzed rice protein (GLUADIN R from BASF), each neutralized as described in example 1, for two terms of 30 minutes.
  • the tape on the right hand side of the blocks prevents exposure of this side to the protein solution and serves as an internal control).
  • the blocks are washed twice with DI water @ 5 minutes, 500 PRM between the two treatments and after the second treatment.
  • the hydrolysate is diluted using a Na 2 HP04 buffer (1.5 mM) and CaCl 2 (2.5 mM). After neutralizing to a pH of 7.5, the solution is filtered and centrifuged. A biocide (CPC 0.1%) and fluoride (in varying amounts as described in table 5) are added to the filtrate, and the microhardness assay is carried out as described above.
  • Etched enamels treated with hydrolysate + fluoride have higher remineralization% compared to the samples treated with fluoride alone. Test are also run using alpha-fetoprotein (AFP) for comparison to the plant protein hydrolysates.
  • AFP alpha-fetoprotein
  • Bovine enamel blocks prepared in accordance with Example 1 are prescreened, to select specimens with (i) scratch free enamel surface and (ii) KH > 300, measuring microhardness as described in Example 3.
  • the selected enamel blocks are then the enamel blocks are pre-treated and subjected to 4 day cycling as described below, using DI water (negative control), 500 ppm F (positive control) and 0.2% wheat hydrolysate (Gluadin W20) + 500 ppm F (test material) prepared as described in the previous example.
  • the microhardness of the enamel blocks is measured again as final (MHf mal ).
  • Enamel blocks are prepared as in Example 1. Each enamel block is sanitized in ethanol twice then washed in sterile DI water three times. Then each enamel block is pre-incubated in saliva supernatant at 4°C overnight to form pellicle on the enamel surface.
  • Unstimulated whole saliva is collected from donors, who refrain from eating and oral hygiene in the morning.
  • the saliva is pooled and centrifuged at 8000 rpm for 10 minutes.
  • the resulting salivary supernatant is decanted into a new sterile tube, and mixed with 1.5% Tryptic soy broth (TSB) at 2: 1 ratio (2 parts saliva supernatant and 1 part TSB).
  • TBS Tryptic soy broth
  • the sediment is washed once using sterile DI water and centrifuged at 8000 rpm for 10 minutes.
  • the water supernatant is removed.
  • Sterile sucrose solution is added to a final concentration of 0.2% for first experiment and 0.4% for the second experiment (level of sucrose is increased in the second experiment to increase de-mineralization level).
  • This mixture represents the reaction mixture.
  • This reaction mixture serves as a demineralization and remineralization solution, since bacteria in saliva sediment will slowly metabolize sucrose to produce acid.
  • Enamel blocks are transferred into a 24 well plate with 2 ml of treatment solution
  • Examples 1-3 show that the hydrolyzed wheat protein can enhance the enamel repair property of fluoride.
  • the results of this experiment show that hydrolyzed wheat protein plus fluoride provides higher anti-cavity efficacy than fluoride alone.
  • the table below shows the results from the two studies.
  • the first study is conducted using 0.2% sucrose for bacteria in saliva sediment to metabolize and produce acid.
  • the second study is conducted with same procedure but using 0.4% sucrose.
  • the level of sucrose in the second experiment is increased so as to product more acid, thus increase level of de-mineralization.
  • Results from both of the studies show that 500 ppm F has better anticavity properties compared to DI water, but its anti-cavity property is still improved when mixed with 0.2% wheat hydrolysate.
  • a treatment phase is completed ex vivo.
  • Initial microhardness (MH) measurements are taken on sound, bovine enamel blocks (MHBaseiine).
  • the blocks are then etched with 30% phosphoric acid until there was a 40% change in the microhardness reading from Baseline.
  • the microhardness is recorded as etched (Equation 1, MHEtched).
  • Each etched enamel block is then immersed in a 2 ml solution of pre-treated 0.2% wheat hydrolysate (Gluadin W20) + 500 ppm F prepared as described above, or a 2 ml solution of 500 ppm F, for 30 minutes. After 30 minutes, the blocks are washed twice with DI water at 500 RPM for 5 minutes, and then dried with a paper towel. This treatment cycle is repeated.
  • the blocks are then secured within the designated location on a retainer for placement in the oral cavity of a subject.
  • Six enamel blocks are placed in each retainer. Pre-punched holes on the retainer allow saliva fluid to contact etched enamel and to provide minerals for remineralization.
  • Each subject thus will have six enamel blocks in the retainer in the oral cavity during the study (3 are treated with the 0.2% wheat hydrolysate + 500 ppm F, and 3 are treated with 500 ppm F as control).
  • the treated and control enamel blocks are randomized on the left or right side of the retainer.
  • the retainers are then stored in a refrigerator until Day 1 of the study.
  • Example 6 Mouthwash formulation
  • This example explores whether the surprising efficacy of the wheat hydrolysate in promoting remineralization is seen in a full mouthwash formula containing 0.2% wheat hydrolysate and 225 ppm F.
  • Two different treatment methods are tested: one treatment (for 7 days) or repeated treatment (once/day for 7 days). The results show wheat hydrolysate keeps its remineralization benefit in both one treatment and repeated treatment; and wheat hydrolysate has better repair efficacy in repeated treatment.
  • test mouthwash and a control mouthwash are prepared, comprising the following ingredients:
  • Bovine teeth are cut, ground and polished to get enamel blocks (around 3x3x2 mm).
  • the enamel thickness is 1-2 mm and the dentin thickness is ⁇ lmm thick.
  • the enamel blocks are marked as left (used for treatment) and right side (used as internal control) using pencil. All MH measurements are completed on both left and right side on the enamel surface.
  • Microhardness (Knoop hardness-KH, 50g load) of sound enamels are measured, and the blocks with KH > 300 are chosen. The blocks then are etched with 30% phosphoric acid for 15sec. The KH are measured as etched.
  • the right side of the block is used as internal control, so only the left side of the block is exposed to treatment.
  • the individual block is treated with 1 ml designated treatment solution (test or control mouthwash) for 1 minute. After the 1 minutes of treatment is done, the block is rinsed twice with deionized water for 5 minutes at 500 RPM before it is unwrapped and the UPVC tape removed.
  • the left side is exposed to treatment, while the right side is incubated in artificial saline only.
  • the right side of the block is re- wrapped before the next treatment is started.
  • a - Test mouthwash treat and then incubate in artificial saliva overnight, repeat for 7 days.
  • C - Test mouthwash treat (once), and then incubate in artificial saliva for 7 days.
  • D - control mouthwash treat (once), and then incubate in artificial saliva for 7 days
  • the microhardness is measured and the remineralization percentage is calculated using equation 1 above.

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Abstract

L'invention concerne des compositions de soin buccal comprenant des protéines végétales partiellement hydrolysées, qui sont utiles dans des procédés de réparation ou d'inhibition de l'érosion dentaire, et favorisant la reminéralisation dentaire, et/ou améliorant les effets anti-cavités du fluorure.
EP16860635.8A 2015-10-26 2016-10-25 Produits de soin buccal, et procédés associés Active EP3368005B1 (fr)

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EP3368005A4 (fr) 2019-08-07
JP2018534363A (ja) 2018-11-22
US20180318200A1 (en) 2018-11-08
ZA201802497B (en) 2019-12-18
CN108601956A (zh) 2018-09-28
US20180353416A1 (en) 2018-12-13
KR20180073612A (ko) 2018-07-02
AU2016344348A1 (en) 2018-05-10
KR102813956B1 (ko) 2025-05-28
JP2018531291A (ja) 2018-10-25
CN108601720B (zh) 2022-04-19
CN108601720A (zh) 2018-09-28
BR112018007782A2 (pt) 2018-10-30
AU2016346191B2 (en) 2019-01-31
AU2016344348B2 (en) 2019-01-03
AU2016346191A1 (en) 2018-05-10
MX2018004952A (es) 2018-11-09
ZA201802483B (en) 2019-10-30
JP7109366B2 (ja) 2022-07-29
KR20180071348A (ko) 2018-06-27
WO2017074960A1 (fr) 2017-05-04
EP3368163A4 (fr) 2019-08-07
WO2017074964A1 (fr) 2017-05-04
EP3368163B1 (fr) 2022-08-17
JP7114473B2 (ja) 2022-08-08
MX2018004953A (es) 2018-09-18
BR112018007782B1 (pt) 2021-07-06
BR112018007785B1 (pt) 2021-11-23
EP3368005B1 (fr) 2022-05-11
KR102853539B1 (ko) 2025-09-01
EP3368163A1 (fr) 2018-09-05
BR112018007785A2 (pt) 2018-10-30

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